The long-term goal of the ongoing and proposed research project is to fundamentally innovate organic synthesis such that a wide variety of organic compounds of biological and medicinal significance can be prepared in efficient, selective, practically useful, and economical manners. Critically needed is to keep improving substantially and continuously organic synthesis through introduction of new and superior synthetically useful reactions, protocols, and procedures. In the NIH-supported research project, this goal has been pursued primarily through active and judicious incorporation of fundamentally superior reactions employing transition metals and their complexes primarily as catalysts, such as the Pd-catalyzed cross-coupling and the Zr-catalyzed carboalumination of alkynes. During the current grant period, the Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction hereafter) discovered by the PI has been developed into a general and potentially useful asymmetric carbon-carbon bond-formation reaction. Thus, the use of the ZACA reaction in target-guided development of protocols and procedures for the synthesis of chiral organic compounds, especially those alkenes, oligoenes, oligoenynes that contain 1 or more proximal asymmetric carbon centers is 1 of the main specific aims of the proposed research. It is fully intended to seek unprecedented high levels of efficiency and selectivity such that the preparation of the desired complex molecules would become genuinely practical for various purposes including medicinal screening and even industrial production. Some of the target compounds whose total syntheses will be attempted during the proposed grant period include mycolactones A and B, delactonmycin, ratjadone, lacrimin A, fluvirucinin A, as well as some (Z)-carotenoids and oligoynes. Equally important in the proposed research are syntheses of those fragments of compounds of biological and medicinal interest that are highly pertinent to the proposed methodological investigations. Being considered for this purpose are discodermolide, hennoxazole A, zincophorin, roselipins, apoptolidin, nafuredin, caIlystatin A, milbemycin B3, calyculin A, and amphotericin B. [unreadable] [unreadable] [unreadable]